CA2112047A1 - Antiretroviral hydrazine derivatives - Google Patents
Antiretroviral hydrazine derivativesInfo
- Publication number
- CA2112047A1 CA2112047A1 CA002112047A CA2112047A CA2112047A1 CA 2112047 A1 CA2112047 A1 CA 2112047A1 CA 002112047 A CA002112047 A CA 002112047A CA 2112047 A CA2112047 A CA 2112047A CA 2112047 A1 CA2112047 A1 CA 2112047A1
- Authority
- CA
- Canada
- Prior art keywords
- valyl
- amino
- phenyl
- acid
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000000798 anti-retroviral effect Effects 0.000 title abstract description 7
- 150000002429 hydrazines Chemical class 0.000 title description 4
- -1 Hydrazine Derivatives Compounds Chemical class 0.000 claims abstract description 795
- 150000001875 compounds Chemical class 0.000 claims abstract description 246
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 138
- 150000003839 salts Chemical class 0.000 claims abstract description 108
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 84
- 239000001257 hydrogen Substances 0.000 claims abstract description 84
- 125000003118 aryl group Chemical group 0.000 claims abstract description 50
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 48
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 42
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 31
- 125000002252 acyl group Chemical group 0.000 claims abstract description 31
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 27
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims abstract description 23
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 13
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims abstract 4
- 125000000217 alkyl group Chemical group 0.000 claims description 189
- 125000001589 carboacyl group Chemical group 0.000 claims description 173
- 239000002253 acid Substances 0.000 claims description 131
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 108
- 238000000034 method Methods 0.000 claims description 104
- 238000006243 chemical reaction Methods 0.000 claims description 88
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 80
- 229940024606 amino acid Drugs 0.000 claims description 70
- 235000001014 amino acid Nutrition 0.000 claims description 65
- 125000003545 alkoxy group Chemical group 0.000 claims description 62
- 230000008569 process Effects 0.000 claims description 60
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 59
- 229910052736 halogen Inorganic materials 0.000 claims description 58
- 150000001413 amino acids Chemical class 0.000 claims description 56
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 55
- 150000002367 halogens Chemical class 0.000 claims description 54
- 125000001424 substituent group Chemical group 0.000 claims description 53
- 125000006239 protecting group Chemical group 0.000 claims description 52
- 125000004432 carbon atom Chemical group C* 0.000 claims description 51
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
- 229950003188 isovaleryl diethylamide Drugs 0.000 claims description 46
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 43
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 42
- 229910052757 nitrogen Inorganic materials 0.000 claims description 42
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 38
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 34
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 34
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 33
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 33
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 32
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 32
- 125000003277 amino group Chemical group 0.000 claims description 31
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 30
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 29
- 239000007858 starting material Substances 0.000 claims description 27
- 229960004295 valine Drugs 0.000 claims description 27
- 239000004474 valine Substances 0.000 claims description 27
- 229910052799 carbon Inorganic materials 0.000 claims description 26
- 125000000524 functional group Chemical group 0.000 claims description 26
- 229920006395 saturated elastomer Polymers 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 24
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 23
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
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- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 22
- 125000004076 pyridyl group Chemical group 0.000 claims description 21
- 235000014393 valine Nutrition 0.000 claims description 21
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 20
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 125000005493 quinolyl group Chemical group 0.000 claims description 20
- 125000002541 furyl group Chemical group 0.000 claims description 19
- 125000002883 imidazolyl group Chemical group 0.000 claims description 19
- 125000001041 indolyl group Chemical group 0.000 claims description 19
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 19
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 19
- 125000001544 thienyl group Chemical group 0.000 claims description 19
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 18
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 18
- 125000002971 oxazolyl group Chemical group 0.000 claims description 18
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 18
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 18
- 125000000335 thiazolyl group Chemical group 0.000 claims description 18
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 17
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- 125000002757 morpholinyl group Chemical group 0.000 claims description 17
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 16
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- 235000004279 alanine Nutrition 0.000 claims description 16
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- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 16
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- 125000004430 oxygen atom Chemical group O* 0.000 claims description 16
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 16
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 15
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 15
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- 125000006307 alkoxy benzyl group Chemical group 0.000 claims description 15
- 229960001230 asparagine Drugs 0.000 claims description 15
- 235000005772 leucine Nutrition 0.000 claims description 15
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 15
- 235000008729 phenylalanine Nutrition 0.000 claims description 15
- 229960005190 phenylalanine Drugs 0.000 claims description 15
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 14
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 14
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- 235000013922 glutamic acid Nutrition 0.000 claims description 14
- 229960002989 glutamic acid Drugs 0.000 claims description 14
- 239000004220 glutamic acid Substances 0.000 claims description 14
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 13
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 13
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 13
- OQEBBZSWEGYTPG-UHFFFAOYSA-N 3-aminobutanoic acid Chemical compound CC(N)CC(O)=O OQEBBZSWEGYTPG-UHFFFAOYSA-N 0.000 claims description 12
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 12
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- QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 claims description 12
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- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
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- BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 claims description 10
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 claims description 10
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- 150000002440 hydroxy compounds Chemical class 0.000 claims description 3
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 3
- LQZPOKVXIDIVDK-FXZOGHEHSA-N 4-[(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl]oxy-4-oxobutanoic acid Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(=O)CCC(O)=O)C1=CC=CC=C1 LQZPOKVXIDIVDK-FXZOGHEHSA-N 0.000 claims description 2
- UWYLKKYPPYGWHO-QMMMHVTISA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] 2-(dimethylamino)acetate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(=O)CN(C)C)C1=CC=CC=C1 UWYLKKYPPYGWHO-QMMMHVTISA-N 0.000 claims description 2
- MXYYRWGONFUEDB-ZHTHUIBPSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] 2-(methylamino)acetate Chemical compound C([C@H](OC(=O)CNC)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)C)N(NC(=O)[C@@H](NC(=O)OC)C(C)C)CC1CCCCC1 MXYYRWGONFUEDB-ZHTHUIBPSA-N 0.000 claims description 2
- QSZUQNCDKFBAFM-VEVNFNBLSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] decanoate Chemical compound C([C@H](OC(=O)CCCCCCCCC)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)C)N(NC(=O)[C@@H](NC(=O)OC)C(C)C)CC1CCCCC1 QSZUQNCDKFBAFM-VEVNFNBLSA-N 0.000 claims description 2
- ZMIDKLHVCHJVRM-MJYVRLNOSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] dodecanoate Chemical compound C([C@H](OC(=O)CCCCCCCCCCC)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)C)N(NC(=O)[C@@H](NC(=O)OC)C(C)C)CC1CCCCC1 ZMIDKLHVCHJVRM-MJYVRLNOSA-N 0.000 claims description 2
- FZAZJVGSZXAWSS-IIFAZUGRSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] octanoate Chemical compound C([C@H](OC(=O)CCCCCCC)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)C)N(NC(=O)[C@@H](NC(=O)OC)C(C)C)CC1CCCCC1 FZAZJVGSZXAWSS-IIFAZUGRSA-N 0.000 claims description 2
- DHKWBEFMSMYGGY-ZYADHFCISA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] quinoline-2-carboxylate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 DHKWBEFMSMYGGY-ZYADHFCISA-N 0.000 claims description 2
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 claims 4
- CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical group N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 claims 4
- OGNSCSPNOLGXSM-UHFFFAOYSA-N 2,4-diaminobutyric acid Chemical compound NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 claims 3
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- ICIYLFRYCOQNEV-KRCBVYEFSA-N (2s)-2-acetamido-n-[(2s,3s)-4-[[[(2s)-2-acetamido-3-methylbutanoyl]amino]-[(4-methoxyphenyl)methyl]amino]-3-hydroxy-1-phenylbutan-2-yl]-3-methylbutanamide Chemical compound C1=CC(OC)=CC=C1CN(NC(=O)[C@@H](NC(C)=O)C(C)C)C[C@H](O)[C@@H](NC(=O)[C@@H](NC(C)=O)C(C)C)CC1=CC=CC=C1 ICIYLFRYCOQNEV-KRCBVYEFSA-N 0.000 claims 1
- ZNCWISAEUYFUMS-YVYLOCOQSA-N (2s)-n-[(2s,3s)-4-[cyclohexylmethyl-[[(2s)-2-[[2-(2-methoxyethoxy)acetyl]amino]-3-methylbutanoyl]amino]amino]-3-hydroxy-1-phenylbutan-2-yl]-2-[[2-(2-methoxyethoxy)acetyl]amino]-3-methylbutanamide Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)COCCOC)[C@@H](O)CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)COCCOC)C(C)C)C1=CC=CC=C1 ZNCWISAEUYFUMS-YVYLOCOQSA-N 0.000 claims 1
- 125000006789 (C3-C7) alkenyloxycarbonyl group Chemical group 0.000 claims 1
- SXGMVGOVILIERA-UHFFFAOYSA-N 2,3-diaminobutanoic acid Chemical compound CC(N)C(N)C(O)=O SXGMVGOVILIERA-UHFFFAOYSA-N 0.000 claims 1
- COLBQNJWCBUKHT-QKUYTOGTSA-N C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(=O)[C@H]1NCCC1)C1=CC=CC=C1 Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(=O)[C@H]1NCCC1)C1=CC=CC=C1 COLBQNJWCBUKHT-QKUYTOGTSA-N 0.000 claims 1
- XEGSVIXUZXEWLG-NSOVKSMOSA-N [(2s,3s)-1-[cyclohexylmethyl-[(2-methylpropan-2-yl)oxycarbonylamino]amino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-phenylbutan-2-yl] pyridine-2-carboxylate Chemical compound C([C@H](NC(=O)OC(C)(C)C)[C@H](CN(CC1CCCCC1)NC(=O)OC(C)(C)C)OC(=O)C=1N=CC=CC=1)C1=CC=CC=C1 XEGSVIXUZXEWLG-NSOVKSMOSA-N 0.000 claims 1
- YUJGIQJUNRVODH-YRCZKMHPSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(2-methoxyethoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(2-methoxyethoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] acetate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OCCOC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OCCOC)C(C)C)OC(C)=O)C1=CC=CC=C1 YUJGIQJUNRVODH-YRCZKMHPSA-N 0.000 claims 1
- ALEFNKJDBGKXND-KRCBVYEFSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] 2,2-dimethylpropanoate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(=O)C(C)(C)C)C1=CC=CC=C1 ALEFNKJDBGKXND-KRCBVYEFSA-N 0.000 claims 1
- RIDCKSVKMOYYOX-ATVIEFTBSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] 2-(1h-imidazol-5-yl)acetate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(=O)CC=1N=CNC=1)C1=CC=CC=C1 RIDCKSVKMOYYOX-ATVIEFTBSA-N 0.000 claims 1
- MPNPLRAKMNMCLV-DZXSPZCNSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] 2-aminoacetate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(=O)CN)C1=CC=CC=C1 MPNPLRAKMNMCLV-DZXSPZCNSA-N 0.000 claims 1
- LZTFINYXSUQEFF-MKJGCKHTSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] 2-pyridin-2-ylacetate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(=O)CC=1N=CC=CC=1)C1=CC=CC=C1 LZTFINYXSUQEFF-MKJGCKHTSA-N 0.000 claims 1
- JXCCEGBZTVYIDF-ULDMLYOQSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] 3-(1h-imidazol-5-yl)propanoate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(=O)CCC=1N=CNC=1)C1=CC=CC=C1 JXCCEGBZTVYIDF-ULDMLYOQSA-N 0.000 claims 1
- FJZOVYJTIXAAKA-ZQWQDMLBSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] 4-(morpholin-4-ylmethyl)benzoate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(=O)C=1C=CC(CN2CCOCC2)=CC=1)C1=CC=CC=C1 FJZOVYJTIXAAKA-ZQWQDMLBSA-N 0.000 claims 1
- AGXSHBOYXYUGQM-DZUOILHNSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] acetate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(C)=O)C1=CC=CC=C1 AGXSHBOYXYUGQM-DZUOILHNSA-N 0.000 claims 1
- BEOLLUONSPHLRO-QMMMHVTISA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] butanoate Chemical compound C([C@H](OC(=O)CCC)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)C)N(NC(=O)[C@@H](NC(=O)OC)C(C)C)CC1CCCCC1 BEOLLUONSPHLRO-QMMMHVTISA-N 0.000 claims 1
- LUJYCVVRYSZHCQ-QBCKSJLUSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] furan-2-carboxylate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(=O)C=1OC=CC=1)C1=CC=CC=C1 LUJYCVVRYSZHCQ-QBCKSJLUSA-N 0.000 claims 1
- RHQFZOLBAHPQPW-ZHTHUIBPSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] propanoate Chemical compound C([C@H](OC(=O)CC)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)C)N(NC(=O)[C@@H](NC(=O)OC)C(C)C)CC1CCCCC1 RHQFZOLBAHPQPW-ZHTHUIBPSA-N 0.000 claims 1
- NXFDIPPTZPFHRJ-YDPTYEFTSA-N [(2s,3s)-1-[cyclohexylmethyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-4-phenylbutan-2-yl] pyridine-2-carboxylate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@H](CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OC)C(C)C)OC(=O)C=1N=CC=CC=1)C1=CC=CC=C1 NXFDIPPTZPFHRJ-YDPTYEFTSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- BIDUMCNGYRDELE-KRCBVYEFSA-N ethyl n-[(2s)-1-[2-[(2s,3s)-3-[[(2s)-2-(ethoxycarbonylamino)-3-methylbutanoyl]amino]-2-hydroxy-4-phenylbutyl]-2-[(4-methoxyphenyl)methyl]hydrazinyl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OCC)[C@@H](O)CN(CC=1C=CC(OC)=CC=1)NC(=O)[C@@H](NC(=O)OCC)C(C)C)C1=CC=CC=C1 BIDUMCNGYRDELE-KRCBVYEFSA-N 0.000 claims 1
- WEFMCBSODKDJFB-DZUOILHNSA-N ethyl n-[(2s)-1-[[(2s,3s)-4-[cyclohexylmethyl-[[(2s)-2-(ethoxycarbonylamino)-3-methylbutanoyl]amino]amino]-3-hydroxy-1-phenylbutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OCC)[C@@H](O)CN(CC1CCCCC1)NC(=O)[C@@H](NC(=O)OCC)C(C)C)C1=CC=CC=C1 WEFMCBSODKDJFB-DZUOILHNSA-N 0.000 claims 1
- JAAGIJIFCMZOAL-JETHTLQNSA-N methyl N-[(3S,5S,6S)-5-[amino(phenyl)methyl]-7-[cyclohexylmethyl-[[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-6-hydroxy-2-methyl-4-oxoheptan-3-yl]carbamate Chemical compound NC([C@@H]([C@H](O)CN(NC(=O)[C@H](C(C)C)NC(=O)OC)CC1CCCCC1)C(=O)[C@@H](NC(=O)OC)C(C)C)C1=CC=CC=C1 JAAGIJIFCMZOAL-JETHTLQNSA-N 0.000 claims 1
- VUMKXPNJDITTGF-SUGCFTRWSA-N methyl n-[(2s)-1-[2-[(2s,3s)-3-[[(2s)-4-amino-4-oxo-2-(quinoline-2-carbonylamino)butanoyl]amino]-2-hydroxy-4-phenylbutyl]-2-(cyclohexylmethyl)hydrazinyl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound C([C@@H]([C@@H](O)CN(NC(=O)[C@H](C(C)C)NC(=O)OC)CC1CCCCC1)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 VUMKXPNJDITTGF-SUGCFTRWSA-N 0.000 claims 1
- UAXFDRCHYHQMCC-FWEHEUNISA-N methyl n-[(2s)-1-[[(2s,3s)-3-hydroxy-4-[(4-hydroxyphenyl)methyl-[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]amino]-1-phenylbutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@@H](O)CN(CC=1C=CC(O)=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)C)C1=CC=CC=C1 UAXFDRCHYHQMCC-FWEHEUNISA-N 0.000 claims 1
- VUSQAKGRQKBAAC-LJWNLINESA-N methyl n-[(2s)-1-[[(2s,3s)-3-hydroxy-4-[[[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-[(4-methoxyphenyl)methyl]amino]-1-phenylbutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@@H](O)CN(CC=1C=CC(OC)=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)C)C1=CC=CC=C1 VUSQAKGRQKBAAC-LJWNLINESA-N 0.000 claims 1
- TTYHCGRFQFXCPF-QKDODKLFSA-N methyl n-[(2s)-1-[[(2s,3s)-4-[cyclohexylmethyl-(pyridine-2-carbonylamino)amino]-3-hydroxy-1-phenylbutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)OC)[C@@H](O)CN(CC1CCCCC1)NC(=O)C=1N=CC=CC=1)C1=CC=CC=C1 TTYHCGRFQFXCPF-QKDODKLFSA-N 0.000 claims 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 150000003254 radicals Chemical class 0.000 description 96
- 235000002639 sodium chloride Nutrition 0.000 description 72
- 230000000875 corresponding effect Effects 0.000 description 67
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
- 239000000460 chlorine Substances 0.000 description 43
- 229910052801 chlorine Inorganic materials 0.000 description 43
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 27
- 239000011737 fluorine Substances 0.000 description 27
- 229910052731 fluorine Inorganic materials 0.000 description 27
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 26
- 229910052794 bromium Inorganic materials 0.000 description 26
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 19
- 239000002585 base Substances 0.000 description 19
- 150000002148 esters Chemical class 0.000 description 19
- 229910052751 metal Inorganic materials 0.000 description 19
- 239000002184 metal Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
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- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
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- ZHRJCTFFPOXHTM-LBPRGKRZSA-N methyl n-[(2s)-1-[2-(cyclohexylmethyl)hydrazinyl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)NNCC1CCCCC1 ZHRJCTFFPOXHTM-LBPRGKRZSA-N 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
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- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
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- YWIWIWKNPYGWLT-UHFFFAOYSA-N potassium;pyrrol-1-ide Chemical compound [K+].C=1C=C[N-]C=1 YWIWIWKNPYGWLT-UHFFFAOYSA-N 0.000 description 1
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- 235000019260 propionic acid Nutrition 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 229910001495 sodium tetrafluoroborate Inorganic materials 0.000 description 1
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- 230000007480 spreading Effects 0.000 description 1
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- 229940014800 succinic anhydride Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003455 sulfinic acids Chemical class 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 description 1
- 150000003461 sulfonyl halides Chemical class 0.000 description 1
- 125000005537 sulfoxonium group Chemical group 0.000 description 1
- 150000003464 sulfur compounds Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QSUJAUYJBJRLKV-UHFFFAOYSA-M tetraethylazanium;fluoride Chemical compound [F-].CC[N+](CC)(CC)CC QSUJAUYJBJRLKV-UHFFFAOYSA-M 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000003555 thioacetals Chemical class 0.000 description 1
- 238000007079 thiolysis reaction Methods 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- LXEXBJXDGVGRAR-UHFFFAOYSA-N trichloro(trichlorosilyl)silane Chemical compound Cl[Si](Cl)(Cl)[Si](Cl)(Cl)Cl LXEXBJXDGVGRAR-UHFFFAOYSA-N 0.000 description 1
- ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 description 1
- 239000005052 trichlorosilane Substances 0.000 description 1
- PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 108010020532 tyrosyl-proline Proteins 0.000 description 1
- 238000010518 undesired secondary reaction Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C281/02—Compounds containing any of the groups, e.g. carbazates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C243/10—Hydrazines
- C07C243/12—Hydrazines having nitrogen atoms of hydrazine groups bound to acyclic carbon atoms
- C07C243/14—Hydrazines having nitrogen atoms of hydrazine groups bound to acyclic carbon atoms of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
- C07C243/26—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C243/34—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of a carbon skeleton further substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
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- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
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- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
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- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
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- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Curing Cements, Concrete, And Artificial Stone (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Paints Or Removers (AREA)
- Adhesives Or Adhesive Processes (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Quinoline Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Epoxy Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH394292 | 1992-12-23 | ||
CH3942/92-0 | 1992-12-23 |
Publications (1)
Publication Number | Publication Date |
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CA2112047A1 true CA2112047A1 (en) | 1994-06-24 |
Family
ID=4266802
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002112047A Abandoned CA2112047A1 (en) | 1992-12-23 | 1993-12-21 | Antiretroviral hydrazine derivatives |
Country Status (21)
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5679688A (en) | 1992-03-11 | 1997-10-21 | Narhex Limited | Quinaldoyl-amine derivatives of oxo-and hydroxy-substituted hydrocarbons |
US5888992A (en) | 1992-03-11 | 1999-03-30 | Narhex Limited | Polar substituted hydrocarbons |
US6071895A (en) | 1992-03-11 | 2000-06-06 | Narhex Limited | Polar-substituted hydrocarbons |
US6258806B1 (en) | 1992-03-11 | 2001-07-10 | Narhex Limited | Amine derivatives of oxo- and hydroxy- substituted hydrocarbons |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996005180A1 (en) * | 1994-08-09 | 1996-02-22 | Abbott Laboratories | Retroviral protease inhibiting 1,2,4-triazacycloheptanes |
WO1996028423A1 (fr) * | 1995-03-15 | 1996-09-19 | Sankyo Company, Limited | Composes dipeptidiques de structure ahpba |
US6225345B1 (en) | 1995-11-21 | 2001-05-01 | Novartis Ag | Azahexane derivatives as substrate isosters of retroviral asparate proteases |
US5849911A (en) * | 1996-04-22 | 1998-12-15 | Novartis Finance Corporation | Antivirally active heterocyclic azahexane derivatives |
TW409125B (en) * | 1996-04-22 | 2000-10-21 | Novartis Ag | Antivirally active heterocyclic azahexane derivatives |
ATE213725T1 (de) * | 1996-07-17 | 2002-03-15 | Novartis Ag | Anilinopeptid-derivate |
JP5005351B2 (ja) * | 2003-12-11 | 2012-08-22 | アボット・ラボラトリーズ | Hivプロテアーゼ阻害性化合物 |
ES2574831T3 (es) | 2006-07-21 | 2016-06-22 | Gilead Sciences, Inc. | Inhibidores de la proteasa antivirales |
WO2008011116A2 (en) * | 2006-07-21 | 2008-01-24 | Gilead Sciences, Inc. | Aza-peptide protease inhibitors |
JOP20180009A1 (ar) | 2017-02-06 | 2019-01-30 | Gilead Sciences Inc | مركبات مثبط فيروس hiv |
TWI829205B (zh) | 2018-07-30 | 2024-01-11 | 美商基利科學股份有限公司 | 抗hiv化合物 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE635585A (enrdf_load_stackoverflow) * | 1962-07-30 | |||
US5142056A (en) | 1989-05-23 | 1992-08-25 | Abbott Laboratories | Retroviral protease inhibiting compounds |
US4794109A (en) | 1982-11-16 | 1988-12-27 | Ciba-Geigy Corporation | 6-hydroxy-lower alkylpenem compounds, pharmaceutical preparations that contain these compounds, and the use of the latter |
FI870474A7 (fi) | 1986-02-07 | 1987-08-08 | Ciba Geigy Ag | Med svavelhaltiga grupper substituerade 5-amino-4-hydroxivalerylderivat. |
WO1992008698A1 (en) * | 1990-11-19 | 1992-05-29 | Monsanto Company | Retroviral protease inhibitors |
CA2057369A1 (en) * | 1990-12-17 | 1992-06-18 | Ann E. Decamp | Stereocontrolled production of hydroxyester, hydroxyamide, and lactone compounds from chiral alpha-amino aldehydes |
ES2093237T3 (es) | 1991-07-03 | 1996-12-16 | Ciba Geigy Ag | Derivados de hidrazina farmacologicamente activos y procedimiento para su obtencion. |
EP0532466A3 (en) | 1991-09-12 | 1993-06-16 | Ciba-Geigy Ag | Derivatives of 5-amino-4-hydroxy-hexanoic acid and their therapeutical use |
AU681342B2 (en) * | 1992-03-11 | 1997-08-28 | Narhex Limited | Amine derivatives of oxo- and hydroxy-substitued hydrocarbons |
CA2130754C (en) * | 1992-03-11 | 2005-02-08 | Damian W. Grobelny | Amine derivatives of oxo- and hydroxy-substituted hydrocarbons |
-
1993
- 1993-12-14 DK DK93810879.2T patent/DK0604368T3/da active
- 1993-12-14 ES ES93810879T patent/ES2093394T3/es not_active Expired - Lifetime
- 1993-12-14 DE DE59303870T patent/DE59303870D1/de not_active Expired - Fee Related
- 1993-12-14 AT AT93810879T patent/ATE143004T1/de not_active IP Right Cessation
- 1993-12-14 EP EP93810879A patent/EP0604368B1/de not_active Expired - Lifetime
- 1993-12-17 AU AU52479/93A patent/AU672448B2/en not_active Ceased
- 1993-12-20 FI FI935753A patent/FI935753A7/fi not_active Application Discontinuation
- 1993-12-21 CA CA002112047A patent/CA2112047A1/en not_active Abandoned
- 1993-12-21 CZ CZ932857A patent/CZ285793A3/cs unknown
- 1993-12-21 NZ NZ250535A patent/NZ250535A/en unknown
- 1993-12-21 IL IL10811393A patent/IL108113A0/xx unknown
- 1993-12-21 SK SK1459-93A patent/SK145993A3/sk unknown
- 1993-12-22 NO NO934774A patent/NO180442C/no unknown
- 1993-12-22 HU HU9303722A patent/HUT66494A/hu unknown
- 1993-12-22 PL PL93301611A patent/PL301611A1/xx unknown
- 1993-12-22 JP JP5324735A patent/JPH06279386A/ja active Pending
- 1993-12-22 ZA ZA939610A patent/ZA939610B/xx unknown
- 1993-12-22 CN CN93112990A patent/CN1093701A/zh active Pending
- 1993-12-23 KR KR1019930029242A patent/KR940014306A/ko not_active Withdrawn
- 1993-12-23 MA MA23378A patent/MA23068A1/fr unknown
-
1996
- 1996-10-04 GR GR960402614T patent/GR3021263T3/el unknown
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5679688A (en) | 1992-03-11 | 1997-10-21 | Narhex Limited | Quinaldoyl-amine derivatives of oxo-and hydroxy-substituted hydrocarbons |
US5888992A (en) | 1992-03-11 | 1999-03-30 | Narhex Limited | Polar substituted hydrocarbons |
US5942504A (en) | 1992-03-11 | 1999-08-24 | Narhex Limited | Amine derivatives of oxo- and hydroxy- substituted hydrocarbons |
US6071895A (en) | 1992-03-11 | 2000-06-06 | Narhex Limited | Polar-substituted hydrocarbons |
US6258806B1 (en) | 1992-03-11 | 2001-07-10 | Narhex Limited | Amine derivatives of oxo- and hydroxy- substituted hydrocarbons |
Also Published As
Publication number | Publication date |
---|---|
SK145993A3 (en) | 1994-08-10 |
PL301611A1 (en) | 1994-06-27 |
FI935753A7 (fi) | 1994-06-24 |
MA23068A1 (fr) | 1994-07-01 |
IL108113A0 (en) | 1994-04-12 |
ZA939610B (en) | 1994-06-23 |
NO180442C (no) | 1997-04-23 |
CZ285793A3 (en) | 1994-07-13 |
ATE143004T1 (de) | 1996-10-15 |
AU5247993A (en) | 1994-07-07 |
HU9303722D0 (en) | 1994-04-28 |
DK0604368T3 (enrdf_load_stackoverflow) | 1997-02-24 |
CN1093701A (zh) | 1994-10-19 |
JPH06279386A (ja) | 1994-10-04 |
FI935753A0 (fi) | 1993-12-20 |
DE59303870D1 (de) | 1996-10-24 |
NO934774L (no) | 1994-06-24 |
EP0604368A1 (de) | 1994-06-29 |
KR940014306A (ko) | 1994-07-18 |
NO934774D0 (no) | 1993-12-22 |
EP0604368B1 (de) | 1996-09-18 |
AU672448B2 (en) | 1996-10-03 |
ES2093394T3 (es) | 1996-12-16 |
NZ250535A (en) | 1995-11-27 |
GR3021263T3 (en) | 1997-01-31 |
HUT66494A (en) | 1994-11-28 |
NO180442B (no) | 1997-01-13 |
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